Biomedical subjects

M Janghorbani

Publications and source records attributed to M Janghorbani.

At least 19 recordsLinked to original sources

PubMed1994

Long-term measurement of organ copper turnover in rats by continuous feeding of a stable isotope.

Utilizing the continuous feeding of a single stable isotope and inductively coupled plasma mass spectrometry, we have developed a method that allows the measurement of organ copper turnover in the rat for at least 8 weeks. Previous methods, based on tracer studies using radioisotopes of copper, were severely limited by the short half-lives of the radioisotopes (12.8 and 61.8 h). Taking advantage of the known ratio of the two naturally occurring stable isotopes of copper (63Cu and 65Cu), dietary copper was replaced by a single isotope of copper (63Cu) for the entire 8-week period. Disappearance of the other isotope (65Cu) from tissues was then monitored as a measure of copper turnover. Because this method is not a tracer study, it has the unique advantage of uniformly labeled physiological and kinetic compartments. Half-lives of individual first-order kinetic compartments within organs and plasma were obtained by analysis of the 8-week copper turnover curves in copper-adequate and copper-restricted rats. Mean decreases in organ copper following 56 days of copper restriction were plasma, 99%; liver, 62%; heart, 3%; muscle, 26%; kidney, 66%; and brain, < 1%. Comparison of normal organ turnover to turnover in copper-restricted rats revealed that this method can be used during periods of severe copper restriction and that copper conservation during these periods is organ specific.

Animals↗

PubMed1994

A prospective population based study of gender differential in mortality from cardiovascular disease and "all causes" in asymptomatic hyperglycaemics.

There have been few prospective epidemiological studies of asymptomatic hyperglycaemia as a risk factor for cardiovascular disease and all causes mortality in women. Gender-specific all causes, cardiovascular disease (CVD), ischaemic heart disease (IHD) and stroke mortality rates and relative risks for asymptomatic hyperglycaemics (top 5%) have been compared to normoglycaemics (bottom 95%) during a mean follow-up of 11.6 years (range 10-14) among 4696 men and 5714 women aged 45-64 at entry in the west of Scotland. Univariate analysis showed that asymptomatic hyperglycaemia was associated with increased risk of all causes, CVD, IHD and stroke mortality in both genders. The degree of this association was greater in women than in men. Using multiple logistic regression (MLR) analysis to take into account differences in age, systolic (SBP) and diastolic blood pressure (DBP), serum cholesterol, body mass index (BMI), and cigarette smoking, high causal blood glucose level was still a significant risk factor for CVD mortality in both genders. It was also a significant risk factor for all causes, IHD and stroke mortality in women but not in men. This study shows that to a lesser degree asymptomatic hyperglycaemia shows the same gender differentials in risk of mortality as have been demonstrated amongst known diabetics.

Cardiovascular Diseases↗

PubMed1993

Measles epidemics in Kerman City, Iran.

In early 1990 an outbreak of measles occurred in Kerman City (population 257,284), Iran. Overall 745 cases were identified, four of whom died (case fatality ratio was 5.4 per thousand). Illness was limited, primarily, to children below 15 years of age: 166 (22.3%) cases were in children under five years, 573 (77%) in those aged between five and 14 years and six (0.8%) were above 15 years of age. The age of the cases ranged from 5 months to 35 years. The age-specific attack rates were 3.9, 1.8, 7.3 and 2.8 per 1,000 for children under 1, 1-4, 5-9 and 10-14 years of age respectively. Overall 14 (1.9%) children with measles were hospitalized for severe complications which consisted mainly of pneumonia, otitis and gastroenteritis. Based on 745 cases with available immunization records, vaccine efficacy was calculated at 88% indicating a slight problem with the cold chain or vaccine. The outbreak was primarily related to low immunization coverage during the last 10 years and indicates the need to improve vaccine coverage with the AIK-C existing vaccine. It also highlights the urgent need for an effective single-dose measles vaccine (Edmondson-Zagreb) for children below nine months of age.

Adolescent↗

PubMed1993

Dysprosium as a nonabsorbable marker for studies of mineral absorption with stable isotope tracers in human subjects.

Two studies were conducted to determine if dysprosium (Dy) could be used as a quantitative fecal marker for studies of zinc-70 (70Zn), copper-65 (65Cu) and magnesium-26 (26Mg) absorption in humans. In the first experiment, Dy excretion was shown to be complete (104 +/- 9%; mean +/- SD, n = 6) and the kinetics of fecal Dy excretion closely paralleled that of 70Zn but not 65Cu. Because of the similarity in 70Zn and Dy excretion kinetics, a method for estimating 70Zn absorption was developed which used 70Zn and Dy data from only the first two stools passed after isotope administration. Average estimates of 70Zn absorption based on the two-stool (partial pool) vs total pool (5-day composite) method were not different (28.0 +/- 5.2 vs 24.4 +/- 4.1%, respectively; means +/- SEM; p > 0.10). In the second study, the same questions was addressed relative to 26Mg absorption. 26Mg and Dy also exhibited nearly identical excretion patterns. Average estimates of 26Mg absorption based on the partial pool vs total pool method were comparable yielding mean values of 22.7 +/- 3.4 vs 23.2 +/- 2.5% and 26.1 +/- 1.8 vs 24.3 +/- 1.8%, respectively, from magnesium-26 oxide (26MgO) and 26Mg glycinate. Advantages and limitations of the partial pool method for estimating mineral absorption are discussed.

Absorption↗

PubMed1993

Gender differential in all-cause and cardiovascular disease mortality.

The gender differential in mortality from all causes, cardiovascular disease (CVD), ischaemic heart disease (IHD) and stroke during the mean follow-up of 11.6 years (range 10-14) was examined among 4696 men and 5714 women aged 45-64 at entry in West of Scotland. Overall mortality was 19.4/1000 person-years of observation among men and 10.8/1000 person-years among women. A multiple logistic regression model was used to control the influence of gender, along with seven other cardiovascular risk factors simultaneously. The risk factors considered were age, systolic (SBP) and diastolic blood pressure (DBP), serum cholesterol, causal blood glucose, body mass index (BMI) and cigarette smoking. Both the prevalence of risk factors and relative mortality risk associated with them differed by gender. Adjustment slightly reduced the gender differential in overall mortality from 2 to 1.9 and from 1.5 to 1.4 for stroke deaths. Multiple logistic regression increased minimally the gender differential for mortality from 2.4 to 2.8 for CVD and from 2.8 to 3.4 for IHD, suggesting that these cardiovascular risk factors do not account for the overall gender difference in mortality rates. Age, SBP, DBP, blood glucose and cigarette smoking were significant predictors of mortality for both genders. Serum cholesterol was a statistically significant predictor of CVD death only for men.

Age Factors↗

PubMed1993

Using the Community Health Index, general practitioner records and the National Health Service Central Registry for a 14 year follow-up of a middle-aged cohort in the west of Scotland.

Record linkage provides an opportunity for relatively inexpensive follow-up in cohort studies. Most studies have used hospital records. However, the Community Health Index, which is a computer-held list of all patients registered with General Practitioners (GPs), now offers opportunities for measuring morbidity at the primary care level. Searching for patients individually on this computer-held Index, we identified 96% of a middle-aged cohort recruited 14 years earlier in a longitudinal study in the West of Scotland. Of these, information was obtained for 78% through direct postal survey and for 87% through contact with GPs. In total, follow-up information was obtained on 903 (92%) of those thought to be alive. The National Health Service Central Registry records data and cause of death and will pass this information to special studies which have 'flagged' individuals' records. Seven per cent of the deaths in this sample had been missed by this process. This may need to be taken into account in previous studies of mortality for this cohort. New studies could expect successful long-term follow-up through record linkage to the Index or the Registry, and automatic record linkage with the Index would be worth investigating.

Cohort Studies↗

PubMed1992

Trends in mortality from stroke in Scotland, 1950-1986.

The Scottish Registrar General's Annual Reports have been used to study trends in mortality from stroke in Scotland during 1950-1986 in those aged 45 to 74. In 1950 the age-adjusted mortality rate was 347.4 per 100,000 population for men and 360.8 for women, falling to 199.6 for men and 155.8 for women in 1986. This downward trend has increased from 1976 for males. The average annual decline in age-adjusted mortality from stroke over the 37-year period was 4.0 per 100,000 in males and 5.5 in females. This reduction in death rates was proportionally higher for women compared with men in all age groups over 55 years. As with cardiovascular deaths, mortality from stroke was lower in the east than in the central region and west of Scotland. The reduction in mortality resulted in a substantial 'saving' of lives, estimated at 12,500 between 1980 and 1984.

Age Factors↗

PubMed1992

Iron absorption and incorporation into red blood cells by very low birth weight infants: studies with the stable isotope 58Fe.

Measurements of iron absorption and incorporation into RBCs were obtained with the stable isotope 58Fe, administered as a reference dose, in 11 premature infants with birth weights between 780 and 1,520 g and gestational ages between 24 and 33 weeks. Each study included a timed stool and urine collection, nasogastric tube administration of a single dose of about 228 micrograms of 58Fe/kg of body weight (as FeSO4, with 10 mg/kg of vitamin C) between feedings, and blood samples before 58Fe (day 1) and then 2 weeks (day 15) later. Gastrointestinal absorption of the 58Fe dose as measured by fecal isotope balance was 41.6 +/- 17.6% (mean +/- SD). However, only 12.0 +/- 9.6% of the 58Fe dose (28.7 +/- 22.3% of the absorbed 58Fe dose) was incorporated into RBCs on day 15. 58Fe absorption and 58Fe incorporation into RBCs on day 15 were significantly correlated with the hemoglobin concentration and reticulocyte count on day 1. Transfusion history did not affect 58Fe absorption or 58Fe incorporation into RBCs. We conclude that concurrent measurement of 58Fe absorption with fecal monitoring and of 58Fe incorporation into RBCs permits a better understanding of the fate of iron ingested by premature infants than either measurement alone.

Algorithms↗

PubMed1991

Correlation between the size of the selenite-exchangeable metabolic pool and total body or liver selenium in rats.

This study explored the quantitative relationship between the size of the selenite-exchangeable metabolic pool (WSe-EMP) and total body or liver Se in rats of varying age and past Se intake. We performed four experiments. In one, weanling rats were fed either a Se-deficient or Se-supplemented diet for 30 d, followed by measurement of WSe-EMP and total body Se. For the other experiments, rats were fed natural sources of Se without added selenite until adult age and then either subjected to acute Se restriction during the 7 d of measurements or maintained on a Se-sufficient diet. For the animals fed the selenite diet, the 7-d average ratio of WSe-EMP:total body Se (Se(end),0) was 0.370 +/- 0.009, which was not significantly different from the corresponding value (0.350 +/- 0.018, P greater than 0.05) for the Se-deficient group. When the group mean values of WSe-EMP were correlated with the corresponding mean values of Se(end),0 for all experiments, we obtained highly linear relations (r2 greater than 0.96). When WSe-EMP for each animal was correlated with the corresponding value of total body endogenous Se (Se(end)) or liver Se(end) (for t = 1 or 7 d), we found equally strong linear relations (r2 greater than or equal to 0.99). We concluded that WSe-EMP accurately reflected total body Se content or the Se content of such organs as liver, regardless of past Se intake, chemical form of Se or age and size of the animals.

Administration, Oral↗

PubMed1991

Selenium absorption and retention by very-low-birth-weight infants: studies with the extrinsic stable isotope tag 74Se.

Measurements of dietary selenium absorption and retention were obtained after administration of a single dose of the extrinsic stable isotope tag 74Se in 20 appropriate for gestational age premature infants with birth weights between 720 and 1,630 g and gestational ages between 26 and 33 weeks. Infants were assigned randomly to receive a standard premature formula (1.34 microgram of Se/dl) or a selenium-supplemented version of that formula (2.03 micrograms of Se/dl). Each study consisted of one feeding that had been extrinsically labeled with 74Se (1.03 microgram/kg) and a timed stool and urine collection. The percent 74Se absorption was 91.2 +/- 5.4% (mean +/- SD) from the standard formula and 86.2 +/- 3.0% from the selenium-supplemented formula (p less than 0.05), but the percent of the absorbed 74Se retained was not different, i.e., 96.6 +/- 2.1% and 95.0 +/- 2.8%, respectively. The percent net absorption and net retention were also not different between the standard and selenium-supplemented formulas; net absorption was 72.7 +/- 18.1% vs. 67.8 +/- 18.8% and net retention was 57.2 +/- 17.6% vs. 53.3 +/- 20.2%, respectively. The percent 74Se absorption and true selenium absorption were significantly correlated with the percent net selenium absorption and net selenium absorption, respectively. We conclude that an extrinsically administered dose of 74Se can be used to study selenium nutrition in growing premature infants.

Birth Weight↗

PubMed1991

Gender-related differences in iron absorption by preadolescent children.

In a study of absorption of iron from meals by preadolescent children (Tanner stage 1), we had noted that erythrocyte incorporation of the extrinsic iron label was somewhat greater by girls than by boys. Although the difference was not significant, the observation seemed to warrant further study. Study A: A precisely determined quantity of ferrous sulfate enriched with the stable isotope 58Fe was given without food to 15 boys and 15 girls (Tanner stage 1) after an overnight fast and was immediately followed by a dose of 70 mg of ascorbic acid. 58Fe enrichment of the erythrocytes was determined by inductively coupled plasma mass spectrometry at baseline and 14 and 42 d after administration of the 58Fe dose. Geometric mean erythrocyte incorporation of the 58Fe label was 35.2% of intake by boys and 45.0% of intake by girls. The difference was significant (analysis of covariance with serum ferritin as covariate, p = 0.035). Study B: Fifteen boys and 15 girls (Tanner stage 1) were fed a breakfast labeled with 58Fe. Geometric mean erythrocyte incorporation of the 58Fe label was 14.8% of intake by boys and 24.7% of intake by girls. The difference was significant (analysis of covariance with serum ferritin as covariate, p = 0.004). Because serum ferritin concentrations were similar in boys and girls, the gender-related difference in iron absorption (as reflected by erythrocyte incorporation of the label) does not appear to be explained by a difference in body stores of iron. We hypothesize that hormonal differences between boys and girls in Tanner stage 1 favor iron absorption by girls.

Ascorbic Acid↗

PubMed1990

The selenite-exchangeable metabolic pool in humans: a new concept for the assessment of selenium status.

An in vivo isotope-dilution approach is considered for assessment of selenium status in human subjects. The approach depends upon the dilution of a single dose of the stable isotope 74SeO3(2-) in the selenite-exchangeable metabolic pool. Data from six metabolic protocols, conducted with healthy North American males, are presented in order to analyze characteristics of this pool. Pool size (WSe-EMP) correlated positively with daily selenium intake in subjects consuming diets of known and variable selenium content. When subjects were given a selenium-adequate or -restricted diet for 30 d, WSe-EMP,7d decreased from 4.49 +/- 0.28 to 3.76 +/- 0.22 mg (p less than 0.05). The corresponding 24-h urinary selenium concentration dropped from 0.556 +/- 0.035 to 0.341 +/- 0.058 mumol/d (means +/- 1 SEM). Route of administration (iv vs po) had no apparent effect on WSe-EMP. In subjects of similar selenium status, the WSe-EMP was reproducible within the expected uncertainties of the method. This approach may be suitable for assessment of selenium status for a wide range of chronic intakes.

Adult↗

PubMed1990

Comparison of the magnitude of the selenite-exchangeable metabolic pool and whole body endogenous selenium in adult rats.

The quantitative relationship between the size of the selenite-exchangeable metabolic pool (WSe-EMP) and whole body endogenous selenium (Seend) was investigated in adult male rats. Two experiments based on multiple labeling with stable isotopes were performed. One focused on short-term (7 d, Expt. 1) and the other on long-term (60 d, Expt. 2) relationships. Rats were fed a Torula yeast diet and water supplemented with [76Se]selenite at 0.1 micrograms Se/mL; the in vivo [74Se]selenite tracer was administered orally. Groups of three or four animals were killed at timed intervals and whole carcass or selected organs were analyzed for the stable isotopes 74Se, 77Se and 82Se with hydride generation/inductively coupled plasma mass spectrometry. The value of WSe-EMP was determined from plasma or urine isotope ratios. In Experiment 1, with plasma as the sampling compartment, WSe-EMP at 24 h was 36.5 +/- 1.2% of the baseline value of whole body endogenous selenium (Seend) and 36.3 +/- 1.8% at 7 d. When urine was the sampling compartment, the corresponding values were 3.9 +/- 0.3% and 43.1 +/- 2.8%, respectively. In Experiment 2, WSe-EMP (plasma) was 38.9 +/- 1.3% of Seend at 7 d, increasing to 45.5 +/- 1.6% at 60 d. The corresponding values for urine as the sampling compartment were 45.5 +/- 2.0% (7 d) and 61.5 +/- 1.7% (60 d), respectively.

Animals↗

PubMed1990

Effect of chronic selenite supplementation on selenium excretion and organ accumulation in rats.

We examined the effect of chronic selenite supplementation on whole body and selected organ selenium (Se) accumulation, urine excretion of total Se and trimethylselenonium ion, and Se balance in adult male rats. Animals were housed in metabolic cages and given either deionized water or water containing 4 micrograms of Se/mL as selenite for 30 d. Absorption of selenite was nearly complete, with only approximately 10% of ingested Se appearing in feces. There was a rapid rise in urinary Se that reached a plateau within a few days and accounted for 54 +/- 2% of the intake. Excretion of trimethylselenonium ion (TMSe) in urine increased rapidly, representing 35-40% of urinary Se in the supplemented animals compared with only 2% for the control group. In one experiment, rats were killed at 30 d and total carcass Se was measured using isotope dilution analysis. Supplemented rats had only a modest increase in whole body Se (94 +/- 4 micrograms Se vs. 66 +/- 3 in controls). Calculation of Se balance in the supplemented rats showed that approximately 35% of ingested Se could not be accounted for by urine plus fecal losses combined with the portion retained in the carcass. The results from this study demonstrate that under the condition of supplementation at 4 micrograms of Se/mL of drinking water, pathways other than urinary and fecal excretion may account for a substantial portion of Se loss.

Absorption↗

PubMed1990

Feasibility of using the stable isotope 25Mg to study Mg metabolism in infants.

The feasibility of using isotopic techniques to study Mg absorption and metabolism was explored in three full-term human infants. 25Mg (98.8 atom %) was administered orally as an in vivo tracer. Fractional 25Mg absorption, isotope retention, endogenous fecal Mg losses, and apparent Mg exchangeable pool size were then determined under three conditions of isotope administration: 1) 20 mg 25Mg, with single feeding; 2) 20 mg 25Mg, distributed over a 24-h period; and 3) 60 mg 25Mg, over a 24-h period. Mg isotope ratios were determined by inductively coupled plasma mass spectrometry. Fractional absorption was increased in all three infants after distributed versus bolus administration at the 20 mg dose; mean (+/- SD) fractional absorption was 64.0 +/- 3.9 versus 54.3 +/- 5.9%, respectively. 25Mg retention was also more in all three infants after distributed administration (55.8 +/- 3.0 versus 44.3 +/- 1.3% of dose). At the 60-mg 25Mg dose, compared to 20 mg, fractional absorption was reduced but absolute isotope absorption more than doubled in all infants; urine isotope losses represented a similar fraction of the absorbed dose, thus, 25Mg retention also more than doubled. Compared to the results of the isotope studies, net Mg absorption and balance were uninfluenced by total Mg intake. Isotope retention with distributed isotope administration resulted in measurable isotopic enrichment of plasma and erythrocytes at 72 h (i.e. plasma isotope enrichment was 6.3-10.2 and 19.2-23.5% for the 20- and 60-mg dose, respectively). With these doses, apparent Mg exchangeable pool size ranged from 5.5 to 7.6 mmol/kg body wt; these values showed a decrease with age both within and between infants.(ABSTRACT TRUNCATED AT 250 WORDS)

Feasibility Studies↗

PubMed1989

Comparison of pneumatic nebulization and hydride generation inductively coupled plasma mass spectrometry for isotopic analysis of selenium.

A comparative investigation between pneumatic nebulization and continuous hydride generation as sample introduction methods for inductively coupled plasma mass spectrometry was carried out for isotopic analysis of selenium in biological samples of interest to human metabolic studies. Experimental parameters known to affect the analytical performance of the system were evaluated: instrument operating parameters, analyte solution/NaBH4 flow rate, and NaBH4 concentration. Signal-to-background ratio was examined for the three stable isotopes 74Se, 77Se, and 82Se. While background count rates for the hydride system were 3-5 times larger than those for the nebulization method, the signal-to-background ratios, normalized for Se concentration, were 30-50 times greater for the hydride system. Absolute detection limits (3 sigma) for the two systems were 20-60 (nebulization) and 0.6-1.8 (hydride) ng of Se. Overall memory of the hydride system was evaluated. Measurable effects were observed within 400 s from switching to analyte solution with differing isotopic composition, only if the sequence of analysis was from high to low ratio (1-4% bias). However, if the sequence was from low to high ratio, precise and linear calibration plots could be obtained over the isotope ratio range of an order of magnitude or higher. While further improvements might lead to potential enhancement of sensitivity and precision of as much as an order of magnitude, the present performance of the hydride system was satisfactory in relation to the requirements of isotopic analysis for metabolic investigations employing 74Se as the in vivo stable isotope tracer.

Isotopes↗

PubMed1989

Isotopic determination of selenium in biological materials with inductively coupled plasma mass spectrometry.

A method for the isotopic determination of selenium in biological matrices is described. The method is based on hydride generation inductively coupled plasma mass spectrometry (ICP-MS). The development is specifically related to the requirements of stable isotope tracer studies in human subjects. The method is based on isotope dilution using 82Se as the in vitro spike and can quantify the 74Se and 77Se contents of samples. It involves wet oxidation (HNO3 - H2O2 or HNO3 - HClO4) of the 82Se-spiked matrix, reduction to selenite by boiling with HCl followed by measurement of the isotope ratios (82Se/77Se and 74Se/77Se) in the gas stream (H2Se) generated from on-line reduction of the sample selenite with NaBH4. Compared with the isotopic signal resulting from a selenite solution containing 5 ng ml-1 of Se, the total sample blank contributions at m/z = 74, 77 and 82 were less than 5% of the respective isotope signal. Worst-case absolute detection limits were 0.2-0.9 ng of Se, depending on the isotope used. Ion beam intensity ratios were measured with an over-all precision [relative standard deviation (RSD)] of 1% for both isotope pairs. Measured ratios (MRa/b) were stable during a given day's operation within the expected precision of the measurements but varied for different days. The magnitude of MRa/b was generally independent of the nature of the matrix. Highly linear relationships were found between ion beam intensity ratios (MRa/b) and the corresponding true isotope ratios for calibration solutions whose isotope ratios had been altered by as much as one order of magnitude.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1989

Experimental selenium restriction in healthy adult humans: changes in selenium metabolism studied with stable-isotope methodology.

Mechanisms responsible for selenium homeostasis were investigated in healthy adult men receiving diets adequate or low in Se (eight subjects per group). The appearance of a stable isotope of Se, 74Se, in plasma, urine, and feces was measured after oral administration of 74Se-selenite. One group received a restricted level of Se (18 +/- 1 micrograms/d) for 30 d, which resulted in a decrease in urinary, fecal, and plasma Se content compared with the group that consumed 119 +/- 1 micrograms/d. Low Se intake also resulted in decreased urinary 74Se excretion (27.2 +/- 1.4% vs 32.5 +/- 2.3% of the absorbed dose for the adequate intake), increased body retention of 74Se (74.8 +/- 3.1% vs 67.6 +/- 3.8% of the absorbed dose for the adequate group), and a contracted selenite-exchangeable metabolic pool (Se-EMP) (9782 micrograms for adequate Se and 6314 micrograms for the low-Se group; p less than or equal to 0.05). Measurement of Se-EMP may provide an additional and sensitive approach for assessing Se nutriture in human subjects.

Absorption↗